Abstract
Converting the single-stranded retroviral RNA into integration-competent double-stranded DNA is achieved through a multi-step process mediated by the virus-coded reverse transcriptase (RT). With the exception that it is restricted to an intracellular life cycle, replication of the Saccharomyces cerevisiae long terminal repeat (LTR)-retrotransposon Ty3 genome is guided by equivalent events that, while generally similar, show many unique and subtle differences relative to the retroviral counterparts. Until only recently, our knowledge of RT structure and function was guided by a vast body of literature on the human immunodeficiency virus (HIV) enzyme. Although the recently-solved structure of Ty3 RT in the presence of an RNA/DNA hybrid adds little in terms of novelty to the mechanistic basis underlying DNA polymerase and ribonuclease H activity, it highlights quite remarkable topological differences between retroviral and LTR-retrotransposon RTs. The theme of overall similarity but distinct differences extends to the priming mechanisms used by Ty3 RT to initiate (−) and (+) strand DNA synthesis. The unique structural organization of the retrotransposon enzyme and interaction with its nucleic acid substrates, with emphasis on polypurine tract (PPT)-primed initiation of (+) strand synthesis, is the subject of this review.
Highlights
Central to the propagation of retroviruses and long terminal repeat (LTR)-retrotransposons is the conversion of their single-stranded RNA genome into integration-competent double-stranded DNA, a multi-step process mediated by the element-encoded reverse transcriptase (RT) [1]
DNA on an RNA template [2,3] to high resolution X-ray structures for human immunodeficiency virus type 1 (HIV-1) RT that have proven instrumental to the success of combination antiviral therapy to stem HIV infection and the progression of acquired immunodeficiency syndrome (AIDS) [1]
RNA-dependent DNA polymerase to be crystallized in the presence of an RNA/DNA hybrid, the goal of data presented in this review is to illustrate the unique topological complexity of Ty3 RT and point out to the reader that our understanding of reverse transcription should be the consequence of comparative studies and not those from a single enzyme
Summary
Central to the propagation of retroviruses and long terminal repeat (LTR)-retrotransposons is the conversion of their single-stranded RNA genome into integration-competent double-stranded DNA, a multi-step process mediated by the element-encoded reverse transcriptase (RT) [1]. Crucial steps in this process involve the use of RNA primers to initiate synthesis of the (−) and (+) strand DNAs (a host-coded transfer RNA (tRNA) and the element-encoded polypurine tract (PPT), respectively). Our understanding of these events has come almost exclusively from retroviruses where, over some. RNA-dependent DNA polymerase to be crystallized in the presence of an RNA/DNA hybrid, the goal of data presented in this review is to illustrate the unique topological complexity of Ty3 RT and point out to the reader that our understanding of reverse transcription should be the consequence of comparative studies and not those from a single enzyme
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